Effect of serotonin(4) (5-HT4) receptor agonists on aldosterone secretion in idiopathic hyperaldosteronism

Serotonin (5-HT) stimulates aldosterone secretion in man through 5-HT4 rece ptors positively coupled to adenylyl cyclase. In particular, it has been sh own that oral administration of a single dose of the 5-HT4 receptor agonist cisapride induces a significant increase in plasma aldosterone levels (PAL ) in healthy volunteers. Idiopathic hyperaldosteronism (IH) is a rare disor der characterized by hypertension, hypokalemia and bilateral adrenal hypers ecretion of aldosterone. In patients with IH, administration of the 5-HT pr ecursor 5-hydroxytryptophan (5-HTP) is followed by a significant increase i n PAL. 5-HTP-induced aldosterone secretion has been attributed to the activ ation of central serotonergic pathways. The aim of the present study was to evaluate the effect of the oral administration of a single dose of cisapri de (10 mg) on aldosterone secretion in 15 patients with IH, in a simple bli nd fashion versus placebo. Cisapride induced a significant increase in PAL but did not affect renin, cortisol and potassium levels. The present study demonstrates that 5-HT4 receptor agonists are able to stimulate aldosterone secretion in patients with IH. These data also indicate that hyperplastic glomerulosa tissue, like normal glomerulosa cells, expresses a functional 5 -HT4 receptor. Therefore, 5-HT4 receptor antagonists may represent a new ap proach in the treatment of primary hyperaldosteronism.